Biopharmaceutical company AC Immune has announced proof-of-concept results from several of its Tau Morphomer candidates, which demonstrated a target-specific reduction of pathological Tau and cognitive and functional improvement in Alzheimer’s disease.

In addition to Tau inhibition, findings also demonstrated a significant reduction of microglia activation and neuroinflammation, another key marker of Alzheimer’s and other neurodegenerative diseases.

Tau Morphomers are the first candidates made using AC Immune’s proprietary Morphomer platform, which generates therapeutic central nervous system (CNS) small molecules with high selectivity for misfolded proteins in multiple proteinopathies.

The small molecules generated bind to misfolded proteins and break up neurotoxic aggregates. They hold promise as CNS-targeting drugs as they also display high levels of brain penetration, bioavailability and metabolic stability, all of which are important for the development of both therapeutic and diagnostic agents for multiple neurodegenerative diseases.

“AC Immune has one of the largest Tau pipelines in the industry and our various therapies intervene at key points in the pathway of Alzheimer’s disease,” said AC Immune CEO Andrea Pfeifer.

“The specifically-designed Tau Morphomers have a unique mode of action, inhibit intracellular Tau pathology the source of Tau spreading and reduce neuroinflammation. Hence, they are well-positioned to be used in mono- and combination therapies of neurodegenerative diseases.”

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The progression of Tau pathology throughout the brain has been linked to the onset and development of cognitive decline. As such, targeting intracellular misfolded and aggregated Tau is widely seen as a crucial means of treating Tau-related diseases.

Tau is one of two proteins recognised as a key characteristic of Alzheimer’s disease, the second being amyloid-beta (Abeta). The disease is identified by neurofibrillary tangles of pathological Tau, and plaque deposits of Abeta.

Tau protein is mainly found in neurons and functions as a component of the cytoskeleton inside the cells. Other Tau-related neurodegenerative diseases include progressive supranuclear palsy and frontotemporal dementia.

AC Immune, which specialises in neurodegenerative diseases, currently has five product candidates in clinical trials. The Swiss company designs and develops therapeutic and diagnostic products which target diseases caused by misfolding proteins.

Its proprietary technology platforms create antibodies, small molecules and vaccines to address a range of neurodegenerative conditions. The most advanced of these is crenezumab, a humanised anti-amyloid-ß monoclonal IgG4 antibody that targets monomeric and aggregated forms of amyloid-ß, with highest affinity for neurotoxic oligomers. Crenezumab is currently in Phase III clinical studies for AD.